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    Genetic risk variants for class switching recombination defects in ataxia-telangiectasia patients

    , Article Journal of Clinical Immunology ; Volume 42, Issue 1 , 2022 , Pages 72-84 ; 02719142 (ISSN) Amirifar, P ; Mehrmohamadi, M ; Ranjouri, M. R ; Akrami, S. M ; Rezaei, N ; Saberi, A ; Yazdani, R ; Abolhassani, H ; Aghamohammadi, A ; Sharif University of Technology
    Springer  2022
    Background: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ataxia telangiectasia mutated (ATM) gene. A-T patients manifest considerable variability in clinical and immunological features, suggesting the presence of genetic modifying factors. A striking heterogeneity has been observed in class switching recombination (CSR) in A-T patients which cannot be explained by the severity of ATM mutations. Methods: To investigate the cause of variable CSR in A-T patients, we applied whole-exome sequencing (WES) in 20 A-T patients consisting of 10 cases with CSR defect (CSR-D) and 10 controls with normal CSR (CSR-N). Comparative analyses on modifier... 

    CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in ex vivo-expanded human T cells

    , Article BioImpacts ; Volume 12, Issue 4 , 2022 , Pages 337-347 ; 22285652 (ISSN) Azadbakht, M ; Sayadmanesh, A ; Nazer, N ; Ahmadi, A ; Hemmati, S ; Mohammadzade, H ; Ebrahimi, M ; Baharvand, H ; Khalaj, B ; Aghamaali, M. R ; Basiri, M ; Sharif University of Technology
    Tabriz University of Medical Sciences  2022
    Introduction: B lymphocyte-induced maturation protein 1 (BLIMP1) encoded by the positive regulatory domain 1 gene (PRDM1), is a key regulator in T cell differentiation in mouse models. BLIMP1-deficiency results in a lower effector phenotype and a higher memory phenotype. Methods: In this study, we aimed to determine the role of transcription factor BLIMP1 in human T cell differentiation. Specifically, we investigated the role of BLIMP1 in memory differentiation and exhaustion of human T cells. We used CRISPR interference (CRISPRi) to knock-down BLIMP1 and investigated the differential expressions of T cell memory and exhaustion markers in BLIMP1-deficient T cells in comparison with... 

    The metabolome profiling of obese and non-obese individuals: Metabolically healthy obese and unhealthy non-obese paradox

    , Article Iranian Journal of Basic Medical Sciences ; Volume 23, Issue 2 , 2020 , Pages 186-194 Chashmniam, S ; Madani, N. H ; Ghoochani, B. F. N. M ; Safari Alighiarloo, N ; Khamseh, M. E ; Sharif University of Technology
    Mashhad University of Medical Sciences  2020
    Objective(s): The molecular basis of “metabolically healthy obese” and “metabolically unhealthy non-obese” phenotypes is not fully understood. Our objective was to identify metabolite patterns differing in obese (metabolically healthy vs unhealthy (MHO vs MUHO)) and non-obese (metabolically healthy vs unhealthy (MHNO vs MUHNO)) individuals. Materials and Methods: This case-control study was performed on 86 subjects stratified into four groups using anthropometric and clinical measurements: MHO (21), MUHO (21), MHNO (22), and MUHNO (22). Serum metabolites were profiled using nuclear magnetic resonance (NMR). Multivariate analysis was applied to uncover discriminant metabolites, and enrichment... 

    CytoGTA: a cytoscape plugin for identifying discriminative subnetwork markers using a game theoretic approach

    , Article PLoS ONE ; Volume 12, Issue 10 , 2017 ; 19326203 (ISSN) Farahmand, S ; Foroughmand Araabi, M. H ; Goliaei, S ; Razaghi Moghadam, Z ; Sharif University of Technology
    In recent years, analyzing genome-wide expression profiles to find genetic markers has received much attention as a challenging field of research aiming at unveiling biological mechanisms behind complex disorders. The identification of reliable and reproducible markers has lately been achieved by integrating genome-scale functional relationships and transcriptome datasets, and a number of algorithms have been developed to support this strategy. In this paper, we present a promising and easily applicable tool to accomplish this goal, namely CytoGTA, which is a Cytoscape plug-in that relies on an optimistic game theoretic approach (GTA) for identifying subnetwork markers. Given transcriptomic... 

    Unraveling cancer metastatic cascade using microfluidics-based technologies

    , Article Biophysical Reviews ; Volume 14, Issue 2 , 2022 , Pages 517-543 ; 18672450 (ISSN) Hakim, M ; Kermanshah, L ; Abouali, H ; Hashemi, H. M ; Yari, A ; Khorasheh, F ; Alemzadeh, I ; Vossoughi, M ; Sharif University of Technology
    Springer Science and Business Media Deutschland GmbH  2022
    Cancer has long been a leading cause of death. The primary tumor, however, is not the main cause of death in more than 90% of cases. It is the complex process of metastasis that makes cancer deadly. The invasion metastasis cascade is the multi-step biological process of cancer cell dissemination to distant organ sites and adaptation to the new microenvironment site. Unraveling the metastasis process can provide great insight into cancer death prevention or even treatment. Microfluidics is a promising platform, that provides a wide range of applications in metastasis-related investigations. Cell culture microfluidic technologies for in vitro modeling of cancer tissues with fluid flow and the... 

    Inferring causal molecular networks: Empirical assessment through a community-based effort

    , Article Nature Methods ; Volume 13, Issue 4 , 2016 , Pages 310-322 ; 15487091 (ISSN) Hill, S. M ; Heiser, L.M ; Cokelaer, T ; Linger, M ; Nesser, N. K ; Carlin, D. E ; Zhang, Y ; Sokolov, A ; Paull, E. O ; Wong, C. K ; Graim, K ; Bivol, A ; Wang, H ; Zhu, F ; Afsari, B ; Danilova, L. V ; Favorov, A. V ; Lee, W. S ; Taylor, D ; Hu, C. W ; Long, B. L ; Noren, D. P ; Bisberg, A. J ; Mills, G. B ; Gray, J. W ; Kellen, M ; Norman, T ; Friend, S ; Qutub, A. A ; Fertig, E. J ; Guan, Y ; Song, M ; Stuart, J. M ; Spellman, P. T ; Koeppl, H ; Stolovitzky, G ; Saez Rodriguez, J ; Mukherjee, S ; Afsari, B ; Al-Ouran, R ; Anton, B ; Arodz, T ; Askari Sichani, O ; Bagheri, N ; Berlow, N ; Bisberg, A. J ; Bivol, A ; Bohler, A ; Bonet, J ; Bonneau, R ; Budak, G ; Bunescu, R ; Caglar, M ; Cai, B ; Cai, C ; Carlin, D. E ; Carlon, A ; Chen, L ; Ciaccio, M. F ; Cokelaer, T ; Cooper, G ; Coort, S ; Creighton, C. J ; Daneshmand, S. M. H ; De La Fuente, A ; Di Camillo, B ; Danilova, L. V ; Dutta-Moscato, J ; Emmett, K ; Evelo, C ; Fassia, M. K. H ; Favorov, A. V ; Fertig, E. J ; Finkle, J. D ; Finotello, F ; Friend, S ; Gao, X ; Gao, J ; Garcia Garcia, J ; Ghosh, S ; Giaretta, A ; Graim, K ; Gray, J. W ; Großeholz, R ; Guan, Y ; Guinney, J ; Hafemeister, C ; Hahn, O ; Haider, S ; Hase, T ; Heiser, L. M ; Hill, S. M ; Hodgson, J ; Hoff, B ; Hsu, C. H ; Hu, C. W ; Hu, Y ; Huang, X ; Jalili, M ; Jiang, X ; Kacprowski, T ; Kaderali, L ; Kang, M ; Kannan, V ; Kellen, M ; Kikuchi, K ; Kim, D. C ; Kitano, H ; Knapp, B ; Komatsoulis, G ; Koeppl, H ; Krämer, A ; Kursa, M. B ; Kutmon, M ; Lee, W. S ; Li, Y ; Liang, X ; Liu, Z ; Liu, Y ; Long, B. L ; Lu, S ; Lu, X ; Manfrini, M ; Matos, M. R. A ; Meerzaman, D ; Mills, G. B ; Min, W ; Mukherjee, S ; Müller, C. L ; Neapolitan, R. E ; Nesser, N. K ; Noren, D. P ; Norman, T ; Oliva, B ; Opiyo, S. O ; Pal, R ; Palinkas, A ; Paull, E. O ; Planas Iglesias, J ; Poglayen, D ; Qutub, A. A ; Saez Rodriguez, J ; Sambo, F ; Sanavia, T ; Sharifi-Zarchi, A ; Slawek, J ; Sokolov, A ; Song, M ; Spellman, P. T ; Streck, A ; Stolovitzky, G ; Strunz, S ; Stuart, J. M ; Taylor, D ; Tegnér, J ; Thobe, K ; Toffolo, G. M ; Trifoglio, E ; Unger, M ; Wan, Q ; Wang, H ; Welch, L ; Wong, C. K ; Wu, J. J ; Xue, A. Y ; Yamanaka, R ; Yan, C ; Zairis, S ; Zengerling, M ; Zenil, H ; Zhang, S ; Zhang, Y ; Zhu, F ; Zi, Z ; Sharif University of Technology
    Nature Publishing Group  2016
    It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was... 

    Investigating the Baldwin effect on Cartesian Genetic Programming efficiency

    , Article 2008 IEEE Congress on Evolutionary Computation, CEC 2008, Hong Kong, 1 June 2008 through 6 June 2008 ; 2008 , Pages 2360-2364 ; 9781424418237 (ISBN) Khatir, M ; Jahangir, A. H ; Beigy, H ; Sharif University of Technology
    Cartesian Genetic Programming (CGP) has an unusual genotype representation which makes it more efficient than Genetic programming (GP) in digital circuit design problem. However, to the best of our knowledge, all methods used in evolutionary design of digital circuits deal with rugged, complex search space, which results in long running time to obtain successful evolution. Therefore, employing a method to guide evolution in these spaces can facilitate achieving more reasonable results. It has been claimed that a two-step evolutionary scenario caused by benefit and cost of learning called Baldwin effect can guide evolution in the biology and artificial life. Therefore, we have been motivated... 

    Integrating evolutionary game theory into an agent-based model of ductal carcinoma in situ: Role of gap junctions in cancer progression

    , Article Computer Methods and Programs in Biomedicine ; Volume 136 , 2016 , Pages 107-117 ; 01692607 (ISSN) Malekian, N ; Habibi, J ; Zangooei, M. H ; Aghakhani, H ; Sharif University of Technology
    Elsevier Ireland Ltd 
    Background and objective There are many cells with various phenotypic behaviors in cancer interacting with each other. For example, an apoptotic cell may induce apoptosis in adjacent cells. A living cell can also protect cells from undergoing apoptosis and necrosis. These survival and death signals are propagated through interaction pathways between adjacent cells called gap junctions. The function of these signals depends on the cellular context of the cell receiving them. For instance, a receiver cell experiencing a low level of oxygen may interpret a received survival signal as an apoptosis signal. In this study, we examine the effect of these signals on tumor growth. Methods We make an... 

    Discovering dominant pathways and signal-response relationships in signaling networks through nonparametric approaches

    , Article Genomics ; Volume 102, Issue 4 , October , 2013 , Pages 195-201 ; 08887543 (ISSN) Nassiri, I ; Masoudi Nejad, A ; Jalili, M ; Moeini, A ; Sharif University of Technology
    A signaling pathway is a sequence of proteins and passenger molecules that transmits information from the cell surface to target molecules. Understanding signal transduction process requires detailed description of the involved pathways. Several methods and tools resolved this problem by incorporating genomic and proteomic data. However, the difficulty of obtaining prior knowledge of complex signaling networks limited the applicability of these tools. In this study, based on the simulation of signal flow in signaling network, we introduce a method for determining dominant pathways and signal response to stimulations. The model uses topology-weighted transit compartment approach and comprises... 

    An integrated analysis to predict micro-RNAs targeting both stemness and metastasis in breast cancer stem cells

    , Article Journal of Cellular and Molecular Medicine ; Volume 23, Issue 4 , 2019 , Pages 2442-2456 ; 15821838 (ISSN) Rahimi, M ; Sharifi Zarchi, A ; Firouzi, J ; Azimi, M ; Zarghami, N ; Alizadeh, E ; Ebrahimi, M ; Sharif University of Technology
    Blackwell Publishing Inc  2019
    Several evidences support the idea that a small population of tumour cells representing self-renewal potential are involved in initiation, maintenance, metastasis, and outcomes of cancer therapy. Elucidation of microRNAs/genes regulatory networks activated in cancer stem cells (CSCs) is necessary for the identification of new targets for cancer therapy. The aim of the present study was to predict the miRNAs pattern, which can target both metastasis and self-renewal pathways using integration of literature and data mining. For this purpose, mammospheres derived from MCF-7, MDA-MB231, and MDA-MB468 were used as breast CSCs model. They had higher migration, invasion, and colony formation... 

    Combined effects of electric stimulation and microgrooves in cardiac tissue-on-a-chip for drug screening

    , Article Small Methods ; Volume 4, Issue 10 , 2020 Ren, L ; Zhou, X ; Nasiri, R ; Fang, J ; Jiang, X ; Wang, C ; Qu, M ; Ling, H ; Chen, Y ; Xue, Y ; Hartel, M.C ; Tebon, P ; Zhang, S ; Kim, H.-J ; Yuan, X ; Shamloo, A ; Dokmeci, M. R ; Li, S ; Khademhosseini, A ; Ahadian, S ; Sun, W ; Sharif University of Technology
    John Wiley and Sons Inc  2020
    Animal models and traditional cell cultures are essential tools for drug development. However, these platforms can show striking discrepancies in efficacy and side effects when compared to human trials. These differences can lengthen the drug development process and even lead to drug withdrawal from the market. The establishment of preclinical drug screening platforms that have higher relevancy to physiological conditions is desirable to facilitate drug development. Here, a heart-on-a-chip platform, incorporating microgrooves and electrical pulse stimulations to recapitulate the well-aligned structure and synchronous beating of cardiomyocytes (CMs) for drug screening, is reported. Each chip... 

    Image-based cell profiling enhancement via data cleaning methods

    , Article PLoS ONE ; Volume 17, Issue 5 May , 2022 ; 19326203 (ISSN) Rezvani, A ; Bigverdi, M ; Rohban, M. H ; Sharif University of Technology
    Public Library of Science  2022
    With the advent of high-throughput assays, a large number of biological experiments can be carried out. Image-based assays are among the most accessible and inexpensive technologies for this purpose. Indeed, these assays have proved to be effective in characterizing unknown functions of genes and small molecules. Image analysis pipelines have a pivotal role in translating raw images that are captured in such assays into useful and compact representation, also known as measurements. CellProfiler is a popular and commonly used tool for this purpose through providing readily available modules for the cell/nuclei segmentation, and making various measurements, or features, for each cell/nuclei.... 

    Channelopathy-related SCN10A gene variants predict cerebellar dysfunction in multiple sclerosis

    , Article Neurology ; Volume 86, Issue 5 , 2016 , Pages 410-417 ; 00283878 (ISSN) Roostaei, T ; Sadaghiani, S ; Park, M. T. M ; Mashhadi, R ; Nazeri, A ; Noshad, S ; Salehi, M. J ; Naghibzadeh, M ; Moghadasi, A. N ; Owji, M ; Doosti, R ; Hashemi Taheri, A. P ; Rad, A. S ; Azimi, A ; Chakravarty, M. M ; Voineskos, A. N ; Nazeri, A ; Sahraian, M. A ; Sharif University of Technology
    Lippincott Williams and Wilkins 
    Objective: To determine the motor-behavioral and neural correlates of putative functional common variants in the sodium-channel NaV1.8 encoding gene (SCN10A) in vivo in patients with multiple sclerosis (MS). Methods: We recruited 161 patients with relapsing-onset MS and 94 demographically comparable healthy participants. All patients with MS underwent structural MRI and clinical examinations (Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC]). Whole-brain voxel-wise and cerebellar volumetry were performed to assess differences in regional brain volumes between genotype groups. Resting-state fMRI was acquired from 62 patients with MS to evaluate... 

    Integrative Utilization of Microenvironments, Biomaterials and Computational Techniques for Advanced Tissue Engineering

    , Article Journal of Biotechnology ; Volume 212 , 2015 , Pages 71-89 ; 01681656 (ISSN) Shamloo, A ; Mohammadaliha, N ; Mohseni, M ; Sharif University of Technology
    Elsevier  2015
    This review aims to propose the integrative implementation of microfluidic devices, biomaterials, and computational methods that can lead to a significant progress in tissue engineering and regenerative medicine researches. Simultaneous implementation of multiple techniques can be very helpful in addressing biological processes. Providing controllable biochemical and biomechanical cues within artificial extracellular matrix similar to in vivo conditions is crucial in tissue engineering and regenerative medicine researches. Microfluidic devices provide precise spatial and temporal control over cell microenvironment. Moreover, generation of accurate and controllable spatial and temporal... 

    Atorvastatin treatment softens human red blood cells: an optical tweezers study

    , Article Biomedical Optics Express ; Volume 9, Issue 3 , 2018 ; 21567085 (ISSN) Sheikh Hasani, V ; Babaei, M ; Azadbakht, A ; Pazoki Toroudi, H ; Mashaghi, A ; Moosavi Movahedi, A. A ; Seyed Reihani, .N ; Sharif University of Technology
    OSA - The Optical Society  2018
    Optical tweezers are proven indispensable single-cell micro-manipulation and mechanical phenotyping tools. In this study, we have used optical tweezers for measuring the viscoelastic properties of human red blood cells (RBCs). Comparison of the viscoelastic features of the healthy fresh and atorvastatin treated cells revealed that the drug softens the cells. Using a simple modeling approach, we proposed a molecular model that explains the drug-induced softening of the RBC membrane. Our results suggest that direct interactions between the drug and cytoskeletal components underlie the drug-induced softening of the cells. © 2018 Optical Society of America  

    Type V collagen in scar tissue regulates the size of scar after heart injury

    , Article Cell ; Volume 182, Issue 3 , 2020 , Pages 545-562.e23 Yokota, T ; McCourt, J ; Ma, F ; Ren, S ; Li, S ; Kim, T. H ; Kurmangaliyev, Y. Z ; Nasiri, R ; Ahadian, S ; Nguyen, T ; Tan, X. H. M ; Zhou, Y ; Wu, R ; Rodriguez, A ; Cohn, W ; Wang, Y ; Whitelegge, J ; Ryazantsev, S ; Khademhosseini, A ; Teitell, M. A ; Chiou, P. Y ; Birk, D. E ; Rowat, A. C ; Crosbie, R. H ; Pellegrini, M ; Seldin, M ; Lusis, A. J ; Deb, A ; Sharif University of Technology
    Cell Press  2020
    Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces... 

    Hybrid multiscale modeling and prediction of cancer cell behavior

    , Article PLoS ONE ; Volume 12, Issue 8 , 2017 ; 19326203 (ISSN) Zangooei, M. H ; Habibi, J ; Sharif University of Technology
    Public Library of Science  2017
    Background: Understanding cancer development crossing several spatial-temporal scales is of great practical significance to better understand and treat cancers. It is difficult to tackle this challenge with pure biological means. Moreover, hybrid modeling techniques have been proposed that combine the advantages of the continuum and the discrete methods to model multiscale problems. Methods: In light of these problems, we have proposed a new hybrid vascular model to facilitate the multiscale modeling and simulation of cancer development with respect to the agent-based, cellular automata and machine learning methods. The purpose of this simulation is to create a dataset that can be used for... 

    Context-Specific Reconstruction and Gap-Filling of Metabolic Networks by Sparse Reconciliation of Data Inconsistencies

    , M.Sc. Thesis Sharif University of Technology Fathi, Ali (Author) ; Tefagh, Mojtaba (Supervisor)
    With the increasingly collected biological data, appropriate usage of this data is of great importance for understanding and predicting biological systems and has been the aim of experiments and data collections. A famous category of biological data is known as “omics” which refers to transcriptomics, proteomics, metabolomics, and fluxomics, from different cells or tissues in various media and conditions. This set of data is regularly used for tasks such as studying cells and organisms, understanding cell states, cancer prediction, etc. and is of great importance in Systems Biology.In this thesis, we concentrate on studying cells or organisms using such data, where during that process, we...